Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, Shandong 250100, P.R. China.
Mol Med Rep. 2019 Mar;19(3):1919-1925. doi: 10.3892/mmr.2019.9828. Epub 2019 Jan 8.
Atorvastatin (Lipitor™) is a lipid‑lowering agent that is widely used in the treatment of cardiovascular diseases. Previous research has largely focused on its cholesterol‑lowering effects; however, a limited number of studies have investigated the actions of atorvastatin on vascular endothelial cells. In the present study, the effects of various doses of atorvastatin were investigated on human umbilical vein endothelial cells (HUVECs). HUVECs were treated with various concentrations of atorvastatin in serum‑free or serum‑containing medium, and alterations in HUVEC morphology were observed. Cell survival and necrosis rates were evaluated using sulforhodamine B and lactate dehydrogenase assays, respectively. In addition, the protein expression levels of cellular apoptosis and autophagy markers were detected using western blot analysis. The results revealed that HUVEC morphology was altered following treatment with various concentrations of atorvastatin. In addition, autophagy was demonstrated to be induced by atorvastatin treatment at all concentrations, whereas high concentrations appeared to induce apoptosis and suppress the survival of HUVECs. In conclusion, the results of the present study suggested that various doses of atorvastatin may exert differential effects on HUVECs, and high doses may suppress angiogenesis. Therefore, atorvastatin may present a novel potential anti‑tumor therapeutic strategy. However, further studies are required to fully elucidate the association between the dose of atorvastatin and its clinical outcome.
阿托伐他汀(立普妥)是一种广泛用于治疗心血管疾病的降脂药物。先前的研究主要集中在其降低胆固醇的作用上;然而,只有少数研究调查了阿托伐他汀对血管内皮细胞的作用。在本研究中,研究了不同剂量的阿托伐他汀对人脐静脉内皮细胞(HUVEC)的影响。将 HUVEC 用无血清或含血清培养基中的不同浓度的阿托伐他汀处理,并观察 HUVEC 形态的变化。分别使用磺酰罗丹明 B 和乳酸脱氢酶测定法评估细胞存活率和坏死率。此外,还通过 Western blot 分析检测细胞凋亡和自噬标志物的蛋白表达水平。结果表明,用不同浓度的阿托伐他汀处理后,HUVEC 形态发生改变。此外,阿托伐他汀在所有浓度下均诱导自噬,而高浓度似乎诱导细胞凋亡并抑制 HUVEC 的存活。综上所述,本研究结果表明,不同剂量的阿托伐他汀可能对 HUVEC 产生不同的作用,高剂量可能抑制血管生成。因此,阿托伐他汀可能为抗肿瘤治疗提供新的潜在策略。然而,需要进一步研究来充分阐明阿托伐他汀剂量与其临床结局之间的关系。